We plan to assess the influence of gradually imposed, adult-initiated controlled dietary restriction on spontaneous cancerogenesis in A.CA/Sn male mice, an H-2 congenic strain which develops pulmonary tumors and hepatomas. The effect of age at time of initiation of underfeeding will be tested as individually caged mice consuming since weaning a semi-synthetic diet in amounts allowing "normal" growth will be dietarily restricted at either 5 months or l0 months of age. The diets used will supply the same per week amounts of protein (casein), vitamins and salts to all mice but calories will be limited for restricted mice such that they consume 70 percent the per week amount as do controls during the first month of underfeeding and 55 percent thereafter. These diets produce undernutrition not malnutrition. Dietary influences on the aging immune apparatus will be measured with emphasis on immunologic suppressor effects. Mice will be sacrificed for evaluation of several age-sensitive immune indices at l4-l5 and l9-20 months of age. These include: lymphocyte proliferation (alloantigen or mitogenstimulated tritiated thymidine uptake in vitro; colony growth in soft agar), humoral immune response (plaque forming cell levels to sheep erythrocyes following in vitro sensitization and lymphocytoxicity (cytolytic response to an allogeneic tumor following in vitro sensitization). Manipulation of these basic assays will reveal the level of suppressor activity which seems to increase in tumor-bearing hosts and with advancing age. Effects of tumor type on these immunologic parameters will also be determined. This study should further define the efficacy of adult-onset dietary restriction as an inhibitor of spontaneous cancerogenesis that was observed in much earlier studies and not further explored. Thus, we wish to reevaluate this phenomenon using improved diets and feeding strategies with an emphasis on the role of immunologic phenomena.